ClinVar Miner

Submissions for variant NM_000419.5(ITGA2B):c.2338del (p.Glu780fs)

dbSNP: rs2143440696
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Platelet Disorders Variant Curation Expert Panel, ClinGen RCV002254803 SCV002525892 pathogenic Glanzmann thrombasthenia 2022-05-17 reviewed by expert panel curation The NM_000419.5:c.2338del (p.Glu780SerfsTer46) variant in ITGA2B exon 23 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 25/30 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been detected in at least one proband with Glanzmann thrombasthenia. However, it is unclear if the reported proband (GT38, PMID: 19691478) was homozygous for this variant or if a second ITGA2B variant was identified. At least one patient (Patient GT38 in PMID: 19691478) with this variant displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_Moderate). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1, PM2_Supporting, PP4_Moderate. (VCEP specifications version 2; date of approval 05/17/2022)

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